Strategies to improve the outcome of esophagectomy for esophageal cancer

Abstract

Esophageal cancer is the 8th most common type of malignancy in the world. For the past decades the incidence of esophageal cancer has rapidly increased, particularly due to a rise in adenocarcinoma of the esophagus. Yet, worldwide the incidence of esophageal squamous cell carcinoma (ESCC) is highest. Radical surgical resection of the esophagus and the surrounding lymph nodes offers the best chance for cure. Five-year survival rate after curative surgery is around 35%. The general aim of this thesis is to investigate strategies in the field of surgery (Part I), molecular biology (Part II) and diagnostic imaging (Part III) through which the outcome of patients that undergo esophagectomy for esophageal cancer could be improved. Open esophagectomy is accompanied by significant morbidity, predominantly due to cardiopulmonary complications. Minimally invasive esophagectomy has been introduced to reduce this morbidity. Yet, conventional scopic surgery has several disadvantages for the surgeon, such as 2-dimensional view, a disturbed eye-hand-coordination and less degrees of freedom. Robotic systems have been developed to overcome those disadvantages. In part I of this thesis, the results of robot-assisted thoracoscopic esophagectomy (RTE) have been described. This innovative surgical technique has shown to be technically feasible and was associated with low blood loss and a steep learning curve. The robotic system facilitated a precise dissection along the vital mediastinal structures. The median number of dissected lymph nodes was equal to the open approach, but more than the thoracoscopic approach. The disease-free survival after RTE was comparable to open esophagectomy as well. To confirm our data and to assess if long-term oncologic outcome of RTE is comparable to open esophagectomy, more prospective studies are warranted. Neoadjuvant chemotherapy may improve the outcome of esophagectomy by opposing early metastatic spread. A disadvantage of chemotherapy is that it destructs all proliferating cells, including normal healthy cells leading to toxicity. Recently, therapy has been developed that selectively acts on tumor cells by aiming at molecular characteristics of a tumor. The aim of Part II of this thesis was to identify potential molecular markers for targeted therapy in ESCC. Promising targets in ESCC appear mTOR, VEGF, EGFR, Cyclin D1 and COX-2, since they were frequently immunohistochemically overexpressed in our ESCC tissues. Based on the results of the studies described in Part III of this thesis, we have concluded that there neither seems a role for the routine aqueous contrast swallow examination performed after esophagectomy to assess the integrity of the cervical anastomosis nor for the sentinel node biopsy technique in esophageal cancer patients. Various diagnostic modalities are available for diagnosing and staging esophageal cancer. In addition, several surgical techniques are performed during esophageal cancer surgery. It is unknown in what frequencies these different diagnostic modalities and surgical techniques are currently being applied worldwide in the work-up and treatment of esophageal cancer patients. We have therefore initiated an international survey among surgeons with particular interest in esophageal cancer. Significant differences in applied diagnostic modalities and surgical techniques were detected between low- and high-volume surgeons and between surgeons from different continents.